A marked strain-related difference was observed among acetohexamide reductase activities in liver microsomes of male rats. The microsomal enzyme activities in the Fischer-344 (Fischer), Sprague-Dawley (SD) and Wistar strains were 2.58 +/- 0.50, 1.60 +/- 0.44 and 0.79 +/- 0.41 nmol/min/mg protein, respectively. The microsomal enzyme activities in these rat strains were much higher in males than in females, indicating that the microsomal enzyme is a male-specific enzyme. The Wistar-Imamichi (Wistar-IM) strain was found to lack the male-specific microsomal enzyme activity. In Fischer, SD and Wistar strains of testectomized male rats, the microsomal enzyme activities were significantly increased by the treatment with testosterone. However, testosterone treatment was ineffective on the microsomal enzyme activity in the Wistar-IM strain. These results suggest that Wistar-IM rats has a genetic deficiency of the microsomal enzyme. There was no strain-related difference among the cytosolic enzyme activities in male rats. The cytosolic enzyme activities in Fischer and Wistar rats were higher in females than in males.