Clones obtained in soft agar from a Shionogi mouse mammary carcinoma show marked heterogeneity of growth characteristics and sensitivities to androgens. These data pertain to spontaneous growth in the absence of androgens, maximal response to dihydrotestosterone (DHT) and Km values of the stimulatory action of DHT ranging from 0.008 to 10 ng/ml (1,250-fold range). Following 13 months in culture in the presence of 10 nM DHT, recloning of one original cell clone led to an even greater variation of androgen-free growth and of the maximal responses to DHT, while the Km values of DHT action ranged from 0.05 to 10 nM (200-fold range). The present demonstration of a marked heterogeneity of Km values of DHT action in subpopulations of tumors grown in a controlled environment has major implications for the efficient antihormonal treatment of androgen-sensitive diseases such as prostate cancer. Such data indicate that cell clones having a high degree of sensitivity to DHT (androgen-hypersensitive) can continue to grow in the presence of castration levels of androgens, thus suggesting that an antiandrogen is required in order to achieve a more complete androgen blockage and to induce a regression of these androgen-hypersensitive tumors.