To investigate outcome and pathophysiology of central nervous system (CNS) systemic lupus erythematosus (SLE), we prospectively codified all cases of CNS SLE. Eighty-two events occurred in 71 patients. Four events in four patients were due to infection and were excluded. Twelve events occurred in 11 women with positive antinuclear antibody but negative anti-DNA antibody test reactions and no other manifestation of SLE. Of the remaining 66 events (56 patients), 26 events were "isolated" and 40 "complex." Non-CNS SLE was "active" during 47 events and "inactive" during 19 events. "Isolated" CNS events were equally likely in clinically "active" and "inactive" SLE. Patients with active SLE were as likely to have an episodic or remittent course as were patients with inactive SLE. "Complex" events, however, were more likely to have favorable outcome than were "isolated" events. "Isolated" events without focal CT abnormalities, the only component of CNS SLE that can be called diffuse lupus encephalitis, accounted for only 20% of all neurologic events.