Circulating IGF-I is correlated with fitness, but results of prospective exercise training studies have been inconsistent, showing both increases and decreases in IGF-I. We hypothesized that energy balance, often not accounted for, is a regulating variable such that training plus an energy intake deficit would cause a reduction in IGF-I, whereas training plus energy intake excess would lead to an increased IGF-I. To test this, 19 young, healthy men completed a 7-day strenuous exercise program in which they were randomly assigned to either a positive energy balance [overfed (OF), n = 10] or negative energy balance [underfed (UF), n = 9] group. IGF-I (free and total), insulin, and IGF-binding protein-1 were measured before, during, and 1 wk after the training. Weight decreased in the UF subjects and increased in the OF subjects. Free and total IGF-I decreased substantially in the UF group (P < 0.0005 for both), but, in the OF group, IGF-I remained unchanged. The UF group also demonstrated an increase in IGF-binding protein-1 (P < 0.027), whereas glucose levels decreased (P < 0.0005). In contrast, insulin was reduced in both the OF and UF exercise-training groups (P < 0.044). Finally, within 7 days of the cessation of the diet and training regimen, IGF-I and IGF-binding protein-1 in the UF group returned to preintervention levels. We conclude that energy balance during periods of exercise training influences circulating IGF-I and related growth mediators. Exercise-associated mechanisms may inhibit increases in IGF-I early in the course of a training protocol, even in overfed subjects.