The role of TRH on ovine fetal L maturation was studied in 12 euthyroid fetuses (F). Beginning at 127 days, 6 F received 3 daily bolus IV injections (I) of 50 ug TRH and 6 control F received saline (S). All were sacrificed at 130 days. The mean body weight and weight of selected organs were similar. Initially, the mean serum thyroxine ([T4]), triiodothyronine ([T3]) and reverse T3 ([rT3]) levels were similar in both groups. In the S group, mean serum iodothyronine levels were similar throughout the study period. In the TRH group, mean (± SEM) [T4] significantly increased from 12.4 ± 2.0 ug/dl to 20.9 ±2.9 ug/.dl (p<0.01) 8 hours (h) later returning to 12.8 ± 2.0 ug/dl at 24 h. Although there was no significant change in the mean [T3], the mean [rT3] increased from 345 ± 36 ng/dl to 568 ± 109 ng/dl (p<0.05) at 8 h, returning to 379 ± 56 ng/dl at 24 h. Similar changes were seen after the 2nd TRH I but no significant changes were seen following the 3rd I. There was no significant change in the mean serum cortisol level throughout the study period in any S F and 5 of 6 TRH F. The mean L tissue protein, DNA and whole L homogenate PAPase levels, protein/DNA and tracheal fluid L/S were similar in both groups. Histologically, the S group L showed areas of mature L and areas compatible with the canalicular stage of development. The TRH L was homogeneous in its mature state of development. Conclusions: TRH given directly to the euthyroid ovine F during the 3rd trimester 1) appears to affect the mesenchymal portion of the L and accelerates alveolarization; 2) increases serum [T4] and [rT3] but not [T3].