The influence of polyamines (putrescine, spermidine, spermine) on the activity of human platelet soluble guanylate cyclase and stimulation of the enzyme by sodium nitroprusside, YC-1 and their combination was investigated. All polyamines used stimulated the guanylate cyclase activity and potentiated its activation by sodium nitroprusside. The stimulatory effects of sodium nitroprusside and putrescine (or spermine) were additive; spermidine produced a synergistic activation and increased the additive effect. All polyamines investigated inhibited the activation of the enzyme by YC-1 and decreased the synergistic activation of sodium nitroprusside-stimulated guanylate cyclase activity by YC-1 with approximately the same efficiency. The revealed ability of polyamines investigated to potentiate and synergistically increase (similar to YC-1, but less effective) NO-dependent activation of soluble guanylate cyclase represents a new biochemical effect of these compounds, which should be taken into consideration, especially due to the endogenous nature of polyamines. The data obtained suggest, that the specific functions of polyamines in the processes of cell growth and diffentiation may be also related to the ability of these compounds to activate soluble guanylate cyclase and increase cGMP level.