Seventy-four Holstein cows (26 primiparous) were utilized to compare the efficacy and safety of sustained-release versus daily injectable formulations of recombinant bST. Twenty-four control cows were injected biweekly with oil microsphere; 25 cows were injected biweekly with 350 mg of bST microsphere; and 25 cows were injected daily with 10.3 mg of bST. Injections were initiated between wk 4 and 5 of lactation and continued for 280 d. Administration of bST caused a moderate increase in milk and FCM production and improved the efficiency of feed and energy conversions. Most health-related and reproduction-related variables did not differ among treatment groups. However, incidence of teat and udder disorders and feet and leg problems tended to be higher during the 40-wk injection period for the bST-treated cows than for the control cows. Incidence of GnRH therapy and number of days to first service were higher for daily bST-treated cows than for controls. No differences existed between sustained-release and daily bST-treated cows for any parameters monitored.