Polyamines such as protamine sulfate have been widely used clinically to neutralize the anticoagulant effect of excessive heparin. Protamine itself exhibits concentration-dependent anticoagulant and procoagulant effects. This laboratory has earlier reported that acetaldehyde exerts synergistic prolongation of the anticoagulant effect of heparin upon prothrombin time (PT). In the current investigation, it is seen that acetaldehyde, the primary metabolite of ethanol metabolism, reacts synergistically with protamine to effect a prolongation of PT beyond the individual effects of acetaldehyde and protamine on the PT. In an analogous study, the effect of polylysine (1-4K) and acetaldehyde upon activated partial thromboplastin time (APTT) was studied. It was observed that the polylysine (PL) prolonged APTT. When PL was preincubated with plasma at RT for 15 minutes, followed by a further 15 minutes with acetaldehyde, an additional prolongation time was observed. When acetaldehyde was preincubated with plasma prior to the addition of PL, a synergistic APTT was noted. When a PL-acetaldehyde mixture was preincubated prior to the addition to plasma, a drastic reduction in the prolongation of APTT was seen, suggesting that PL and acetaldehyde may detoxify one another by a Schiff base reaction under highly specific conditions.