Problem: In newborn guinea pigs the structural development of the liver was studied with emphasis on changes in the lipid content as related to biochemical parameters. Material and methods: The livers of 149 guinea, pigs (strain Pirbright) up to an age of 21 days were examined. The mothers were grouped in cages and kept as usual (room temperature 22 °C, air humidity 60–70 %, natural light-dark rhythm and commercial standard diet ad libitum, sawdust and straw as bedding). Pregnant animals were placed in individual cages being left there together with their offspring until weaning or sacrification. In this period additional uptake of solid diet was allowed to the young guinea pigs. The animals were bleeded to death in anesthesia (by head stroke). For histological examination tissue samples from the Lobes sinister lateralis were fixed in Barker’s formol or absolute alcohol. The following staining reactions were applied (paraffin embedding or frozen sections): haemalumeosin stain ; PAS-reaction; Sudan III; Sudan black; Best’s carmine (for details on the techniques see Romeis 1968). In biochemical analysis the total lipids of the liver were determined by the isolation methods reported by Folch et 301. (1957). Moreover, in modification of the analytical procedures earlier described (Sallmann 1972 a, b) several fractions of the liver total lipids could be isolated. By dialysis against a rubber membrane a dialysable lipid component (hydrocarbons, triglycerides, incomplete glycerides, cholesterol and free lipid acids) was isolated from the phosphatide fractions. Further separation of the “dialysable” lipids on Florisil columns yielded purified glyceride fractions. The total lipids as well as all components isolated from these were determined gra,vimetrically after removal of the solvents concerned. In biochemical analysis the livers of fetuses 10–12 days an te partum and of young animals up to 53 days were included. Results (see also table 1): The relative liver weight — related to the body weight reduced for that of the gastrointestinal tract — is highest at birth. It is lowered independent of the development of the gastrointestinal tract within a short period, then it remains fairly constant during the rest of the time of observation. On the 1st day abundant lipids are regularly distributed throughout the whole liver lobule (fig. 1). Beginning with the 3rd day the central parts of the lobules are nearly free from lipids, only in the peripheral zones of the lobules lipid augmentation was still observed. Consequently the marked decrease in liver weight is due to the rapid reduction of lipids within the first 3 days of life. These observations are in accordance with the biochemical findings: about 10 days ante partum noticeable storage of lipids occurs in the liver reaching its peak 2 to 3 days after birth (physiological fatty infiltration of the liver during the last days of intrauterine life). In fetal liver tissue predominantly tryglycerides are augmented. In addition to de-novo-synthesis especially the intense transplacental influx of the maternal free fatty acids into the fetal tissue of guinea pigs is suggested to contribute to the enhancement of lipid and lipoproteid synthesis (very low density lipoproteins = VLDL). With respect to their energy metabolism the newborn guinea pigs are obviously dependent on these immediately available lipid stores in the liver during the first few days after birth. This mainly meets with the guinea, pig as it is of high motility already on the 1st postnatal day after a, relatively long period of intrauterine development. The observations concerning liver glycogen can be interpreted in similar way: Within the first few postnatal days the glycogen estimations show strongly positive results throughout the whole liver lobule. On the 3rd and the 4th day the glycogen is predominantly localized mainly in the centrolobular area, however, it still extends fairly deep into the peripheral zones. This pattern of distribution with marked decrease of glycogen in the peripheral zone of the lobule persists until the end of the experimental period.