OBJECTIVE Our previous experience with highly purified plasma-derived factor VIII (pdFVIII) concentrates showed that adult dosage recommendations were not applicable to children. In this study, we compared the in vivo response and recovery of recombinant factor VIII (rFVIII) with those of highly purified pdFVIII concentrate in children with hemophilia A. METHODS Ten boys with severe factor VIII deficiency and no concurrent bleeding episodes participated in a masked, prospective, crossover study comparing factor VIII coagulant activity after infusion of 50 units of pdFVIII and rFVIII products per kilogram of body weight. RESULTS Mean peak factor VIII response with rFVIII was 1.91% +/- 0.14%, significantly better than the response observed with highly purified pdFVIII of 1.5% +/- 0.15% (p = 0.007). Mean peak factor VIII recovery was 100.5% with rFVIII versus 78.7% with pdFVIII (p = 0.007). Positive correlations between response to rFVIII and body surface area (r = 0.734, p = 0.015), body weight (r = 0.762, p = 0.01), and plasma volume (r = 0.659, p = 0.03) were observed. CONCLUSIONS Infusion of rFVIII produced a significantly better response and recovery in vivo than infusion of highly purified pdFVIII in children. The response in children after infusion of rFVIII was similar to the response previously observed in adults.