An outbreak of nosocomial aseptic meningitis involving four renal allograft recipients on the transplant service occurred in July 1986, shortly after the release of the murine monoclonal antibody OKT3 for therapy for acute allograft rejection. No bacteria, fungi, or viruses were isolated from cultures of the cerebrospinal fluid of the four patients. All four had acute allograft rejection treated with OKT3 and developed signs and/or symptoms of meningitis within 72 hours of receiving the drug. To identify potential risk factors, the four patients with aseptic meningitis were compared with 12 patients on the renal transplant service in July 1986 who did not have signs or symptoms of meningitis. The development of aseptic meningitis was strongly associated with administration of OKT3. Because of this association, prospective surveillance of meningitis in patients receiving OKT3 was instituted. From November 1986 to May 1987, three (14%) of 21 patients treated with OKT3 developed aseptic meningitis. The clinical course of aseptic meningitis associated with OKT3 appears to be benign and self-limited. Nonetheless, this observation warrants continued surveillance of OKT3 therapy.