The majority of vasectomized men develop antibodies against different sperm antigens, including protamine. Due to the fact that salmon protamine is used clinically for heparin reversal and that a cross-reactivity has been observed between human and salmon protamine, vasectomized men may be at risk for adverse reactions to protamine sulfate. In order to explore this possibility, serum samples were analyzed for the presence of anti-sperm and anti-protamine antibodies in 20 vasectomized and 20 non-vasectomized men (controls) about to undergo major heart surgery requiring heparin reversal. The patients were closely monitored for any possible reaction following the injection of protamine. Anti-sperm antibodies were detected in the serum of 15 of the vasectomized men whereas only two of the non-vasectomized subjects had this type of antibody. Twenty-five percent of the vasectomized men presented with anti-protamine antibodies; in the control group, none of the patients had developed this type of antibody. Following the administration of protamine sulfate, none of the patients in either group showed any adverse reaction to the drug. It is concluded that vasectomized men are not at increased risk towards adverse reactions following the injection of protamine sulfate.