Rehabilitation programs and research experiments use single-arm protocols in which the contralateral arm is not functional or used as a control limb. This study was interested in determining the hormonal signal impacts of such one- versus two-arm exercise responses that might have an impact on adaptational changes with training. The purpose was to examine the acute hormonal responses to a unilateral and a bilateral upper-body resistance exercise (RE) protocol. A balanced randomized treatment intervention with series time frame for blood collections before and after exercise was used as the basic experimental design. Ten recreationally resistance trained men (18-25 years, 20.4 +/- 1.2 years, 175.6 +/- 4.5 cm, 81.7 +/- 9.3 kg) gave informed consent to participate in the investigation. Each subject performed unilateral (dominant arm only) and bilateral upper-body RE protocol separated by 1 week in a balanced randomized fashion. The RE protocol consisted of 3 sets of 10 repetitions of 5 different dumbbell upper-body exercises at 80% of 1-repetition maximum, and blood samples were obtained before and 5, 15, and 30 minutes immediately postexercise (IP). Blood was obtained and analyzed for lactate, immunoreactive growth hormone (iGH), cortisol (C), total testosterone (T), and insulin concentrations. Total volume of work also was determined for the 2 exercise sessions. Total volume of work performed during the unilateral protocol was 52.1% of that for the bilateral protocol. Both RE protocols elicited a significant (p < or = 0.05) increase in lactate and iGH, but the increase for the bilateral condition was significantly greater. Cortisol decreased significantly during recovery for the unilateral condition. Testosterone was not affected by either protocol. Insulin was significantly increased at IP and 5 minutes postexercise for both conditions.These results indicate that the hormonal responses to dominant-arm unilateral RE is blunted compared to that for bilateral RE. This differential endocrine response is likely a result of the difference in volume between the protocols. It is important to pay attention to the amount of muscle mass utilized in a resistance exercise protocol to optimize endocrine signaling.