Using the Raji cell radioimmunoassay, we have determined circulating immune complex (CIC) levels in 36 patients with prosthetic valves during 38 episodes of fever. Fever resulted from prosthetic valve endocarditis (PVE) in 27 instances and from other causes in 11 instances. Peak initial CIC levels higher than 100 micrograms/mL occurred more frequently in the group with PVE, while peak initial CIC values less than 30 micrograms/mL were more frequent in the control group. Circulating immune complex levels fell substantially with completion of antibiotic therapy in 28 (78%) of the patients with PVE. Late CIC elevations were associated with drug-related rashes and replacement of persistently infected prostheses. Our data suggest that the predictive value of measurement of CIC levels in patients with fever and prosthetic valves is in excluding PVE in patients with CIC levels persisting below 30 micrograms/mL.