Nine patients with an initial onset of symptoms of acute arthritis within the preceding four weeks were enrolled in a prospective serological study with clinical follow-up for six months to two years. Four adults with chronic rheumatoid arthritis and ten healthy adults were similarly studied. Serial titers measured included antibodies to Epstein-Barr virus (EBV) antigens, group B coxsackieviruses, rubella virus, cytomegalovirus, and herpes simplex virus. Serological evidence of active EBV infection was found in four of the patients with acute arthritis, none of the patients with chronic arthritis, and one of the ten healthy adults. There was no similar correlation between acute disease and presence of antibodies to the other viruses tested. We suggest that EBV may cause acute rheumatic illnesses more commonly than is currently appreciated but is probably not involved in the etiology of typical chronic rheumatoid arthritis.