Insulin-like growth factor binding protein (IGF-BP) complexes containing either IGF-I or IGF-II were purified from human plasma and coincubated with human foreskin fibroblasts. Incorporation of [3H]thymidine into fibroblasts was measured to determine the mitogenic effects of the IGF-BP complexes in comparison with purified recombinant IGF-I or IGF-II. The IGF-I-BP complex was shown to have no stimulatory activity when added to cultures at a comparable Non Suppressible Insulin-Like Activity (NSILA) dose level to that of purified recombinant IGF-I which produced maximal stimulation. In contrast, the IGF-II-BP complex produced a similar stimulatory activity to that of purified recombinant IGF-II when added at comparable NSILA doses. NSILA-p, a contaminating factor in the purified preparations of IGF-BP complexes, was shown to have no effect on fibroblast growth. This study suggests that plasma IGF binding proteins may have a differential effect on the stimulatory activities of IGFs I and II on human fibroblasts.