The regulation of delta 6 desaturase activity by environmental temperature changes was studied in the microsomal membranes from female and ovariectomized female rat liver. Female rats adapted at 30-32 C for 20-25 days and then shifted to 13-15 C for 5 days showed an increased delta 6 desaturase system. Ovariectomized rats adapted under the same conditions did not show significant changes in this enzyme. The fatty acid compositions of microsomal phosphatidylcholine showed a decrease in arachidonic acid in female rats at 30 C compared to females at 15 C and ovariectomized rats at both temperatures. These results suggest that a modification of ovaric sex hormone levels might be responsible for the different delta 6 desaturase activity in female rats acclimated at both temperatures. In this regard, serum estradiol radioimmunoassay yielded slight differences between the two groups of female rats, suggesting that estradiol could play a role in the regulation of the delta 6 desaturase. The administration of a pharmacological dose of 17-beta estradiol to female and ovariectomized rats kept at 30 and 15 C decreased the delta 6 microsomal desaturase activity. These data suggest that estradiol levels are involved in the regulation of the delta 6 desaturase during cold adaptation.