To investigate the effect of pregnancy on the course of streptozotocin (STZ) induced diabetes, insulin binding to receptors and glucose transport activity were studied in isolated adipocytes from normal nonpregnant, normal pregnant, STZ-treated nonpregnant and STZ-treated pregnant rats. Experimental diabetes was induced by the administration of 40 mg/kg of STZ, and those exhibiting blood sugar concentrations between 150 and 250 mg/100 ml (198.8 +/- 6.4 mg/100 ml, mean +/- SEM) 7 days after treatment, were then used for the experiments as diabetic animals. Rats were mated at least 10 days after STZ administration. All studies were performed on gestational day 19. Fetuses of the diabetic mothers tended to be heavier than those of the control rats (2.49 +/- 0.31 vs. 2.38 +/- 0.22 g, mean +/- SD), but the difference was not statistically significant. Placental weights were significantly greater in the diabetics than in the controls (0.60 +/- 0.12 vs. 0.48 +/- 0.097 g, mean /+- SD, p less than 0.05). Insulin binding to receptors at an insulin concentration of 0.2 ng/ml was increased by 21% in the STZ-treated nonpregnant group as compared with the untreated non-pregnant group, by 32% in the STZ-treated pregnant group as compared with the untreated pregnant group due to increased receptor affinity without increasing the receptor number. However, no change in insulin binding was detected between the normal nonpregnant and normal pregnant, STZ-treated nonpregnant and STZ-treated pregnant groups. Glucose transport activity was decreased in adipocytes from the normal pregnant group as compared with that of the normal nonpregnant group. The effect was also observed between adipocytes from the sTZ-treated pregnant group and from the STZ-treated nonpregnant group. Adipocytes from rats belonging to either the normal pregnant group or the STZ-treated nonpregnant group showed a similar decrease in glucose transport activity, suggesting an equal effect of pregnancy and mild diabetes on glucose transport. Furthermore, adipocytes from the STZ-treated pregnant group showed the lowest transport activity of the four groups studied, suggesting an additive effect of pregnancy and diabetes on glucose transport activity. In conclusion, although insulin action in isolated adipocytes is reduced by pregnancy whether diabetes is induced or not, insulin binding to receptors is not changed by pregnancy. Thus, the effect on insulin action in adipocytes from diabetic rats as well as normal rats might lie at a site distal to the receptor. Insulin action in isolated adipocytes is reduced additively by pregnancy and diabetes.