This work examined the extent to which progesterone (P) in whole blood is transported in association with red blood cells (RBC) in the rat. The effects of plasma P concentration and changes in the source of whole blood on this association were also assessed. Initially, the RBC uptake of [3H]P was measured in vitro in blood from either adrenalectomized-ovariectomized (Ax-Ox) rats, thus rendered effectively P-free, and from rats at Day 16 of pregnancy. In blood from Ax-Ox rats, almost 10% of [3H]P was located within the RBC fraction, and this percentage increased with the addition of exogenous P (range of mean RBC uptake 9.4-18.9% over a plasma P concentration range of approximately 100-4500 ng/ml). A similar though less marked effect of exogenous P was observed in blood from pregnant rats (mean RBC uptake 11.7-14.8% over a similar plasma P concentration range), suggesting that plasma from pregnant rats had a greater capacity to bind P. To assess the RBC uptake of P in vivo, arterial blood samples were obtained during constant infusion of [3H]P in Day 16 pregnant rats with or without prior P supplementation (20 mg P per day over 4 days). The mean RBC uptake of P in control rats was 18.8 +/- 0.7%, but was reduced (p less than 0.05) to 16.2 +/- 0.5% after P supplementation. This reduction may have been due to the increase in the P-binding capacity of plasma known to occur after P supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)