Primiparous (n = 105) and multiparous (n = 136) Holstein cows were used to evaluate efficacy of sometribove (n-methionyl bovine somatotropin, bST) in a dose titration study. Cows were fed TMR for ad libitum intake, were milked twice daily, and were allocated randomly within parity (1 vs. 2+) to treatments of 0, 250, 500, or 750 mg bST/14 d in a prolonged-release formulation. Subcutaneous injections commenced 60 +/- 3 d postpartum and continued throughout lactation. During a standardized treatment period of 252 d, treatment with increasing dosages of bST increased 3.5% FCM yield in a dose-dependent manner for both primiparous (2.5 kg/d, 10.2%; 3.5 kg/d, 14.3%; and 5.9 kg/d, 24.1%) and multiparous cows (3.1 kg/d, 12.1%; 3.9 kg/d, 15.2%; and 6.8 kg/d, 26.5%). Milk content of fat, protein, lactose, ash, Ca and P, and SCC were not affected by treatment. Over the 252-d treatment period, voluntary intake of energy was increased in bST-treated cows such that BW gain, body condition score, and net energy balance did not differ among treatment groups. Productive efficiency (milk per unit NEL intake corrected for BW change) over the treatment period was significantly increased in a dose-dependent manner for multiparous cows (4.1, 6.8, and 11.0%). Results demonstrated that bST administered in a prolonged-release formulation was efficacious in enhancing milk production and feed efficiency.