Because aggressive encounters are known to affect immune function in rodents, we hypothesized that individual behavior and social experience would contribute importantly to the impact of confrontation on the activity of the complement system (CA) in guinea pigs. CA was determined by lysis of Euglena gracilis cells (triggered by alternative pathway mechanisms). Males with different social experience were used: i) individually housed males (IH), ii) socially less-experienced males (LE), raised in large groups in the absence of adult animals; and iii) socially experienced males (EX) with additional fighting experience. An IH and LE male, respectively, was introduced into a group of EX residents (consisting of one male and two females). During a 26-day confrontation period the behavior of all animals was quantitatively recorded. IH and LE males showed a significant and persistent decrease in CA after confrontation (mean +/- SEM lysed cells/100 cells; IH: -16.5 +/- 4.0, LE: -16.5 +/- 3.5), whereas no significant changes from baseline were observed in EX males (-2.5 +/- 3.0). However, in social situations characterized by unstable dominance, EX males showed a lowered CA (-11.3 +/- 4.0) as well. Plasma cortisol concentrations determined in LE males were significantly elevated 4 h after confrontation but did not correlate with the long-term decrease in CA. The data indicate that the activity of the complement system can be influenced by psychosocial stressors, and suggest the importance of prior social experience for the guinea pig's ability to cope with social conflicts.