Although skeletal muscle is the principal target for androgenic anabolic steroids (AAS) other physiological and behavioral processes are also affected. Wide variations in response to AAS are known to exist in individuals but the genetic basis of this has hardly been explored. Female mice from the A/J and C57BL/6J strains were divided into four experimental groups: CTRL-Sham, housed in a regular mouse cage and subjected to a sham operation mimicking implantation of steroids; CTRL-AAS, mice similarly housed and implanted with a pellet containing stanozolol (release rate, 4.6 mg/kg/day); EX-Sham, sham operated mice housed in a cage with two towers which required mice to climb 1 m to obtain food or water; EX-AAS, mice similarly housed and implanted with a stanozolol pellet. The experimental treatment was initiated at 10 weeks of age and lasted for 7 weeks. Body weight was assessed periodically during the experiment (time effect), systolic blood pressure (BP) and heart rate (HR) were measured after 6 weeks of treatment, and weights of gastrocnemius (GAST), soleus, tibialis anterior (TA), extensor digitorum longus (EDL), quadriceps femoris (QF) and biceps brachii (BB) muscles, heart, liver, kidney and abdominal fat were measured after 7 weeks of treatment. AAS treatment significantly increased weight of GAST (P << 0.001), TA (P < 0.01), EDL (P < 0.01) and QF (P << 0.001) muscles in both of the strains. Several of the measured indices were differentially affected in the two strains by AAS (body weight, Time x Strain x AAS P < 0.02; BP and HR, Strain x AAS P < 0.03 and P < 0.01, respectively). These findings encourage the view that recombinant inbred strains and chromosome substitution strains derived from the A/J and C57BL/6J mice can be utilized to explore the genetic architecture of these interactions in order to elucidate the mechanism underlying both the positive and negative health-related effects of AAS.