Cytological changes were investigated in mammary parenchyma of cows hormonally induced to lactate. Four cows were induced with injections of 17 beta-estradiol plus progesterone (days 1 to 7) and dexamethasone (days 17 to 19). Tissue biopsies were obtained on days 0, 8, 16, and 26; and milking commenced on day 18 or 21 of the treatment period. Mammary tissue of cow A, the most successful animal, showed marked cellular proliferation and differentiation by day 8. By day 16, the parenchyma of cow A had undergone lactogenesis and exhibited histological and ultrastructural characteristics associated with actively secreting mammary tissue. Mammary epithelia of cow D, the least successful animal, showed minimal development by day 8 and ultrastructurally resembled nondifferentiated mammary cells. Mammary parenchyma of cow D had not undergone differentiation and was involuting by day 16. Mammary tissues of cow B and C showed intermediate responses with only slight development by day 16 and only limited areas of secretory activity by day 26. Results suggest that animals successfully induced into lactation undergo critical periods of cellular proliferation and differentiation which unsuccessful animals do not experience. Cytological differences were first evident by day 8, further magnified by day 16 of the treatment period, and subsequently expressed in terms of milk production (peak milk yield equaled 30.5, 10.0, 9.2, and 2.4 kg/day for cows A, B, C, and D).