The dose-response characteristics of three skeletal muscles, three adipose tissue beds, and heart muscle to single i.v. injection of insulin were compared in vivo. Comparisons were made at 8 dose levels spanning the entire range for response by all tissues and for the integrated whole body response as reflected in the rate of disappearance of 3H-2-deoxyglucose from plasma. The insulin-sensitive tissues varied widely with respect to the magnitude of the maximal response and the sensitivity to insulin as judged by the effective dose 50% (ED 50). Among the muscles, a slow-twitch oxidative muscle, soleus, was more sensitive than the fast-twitch glycolytic muscle, extensor digitorum longus (EDL), while a mixed muscle, quadriceps femoris, displayed even lower sensitivity. Heart muscle sensitivity was comparable to EDL. Among the adipose sites, the rank order of sensitivity was subcutaneous greater than epididymal much greater than omental. The threshold for a detectable response to insulin was 0.013 U/kg rat.