Antibodies reactive with the cytoplasm of neurons were found in 41% of SLE patients with active neurologic disease (group I). In contrast, these antibodies were found in 24% of lupus patients with past history of neurologic disease (group II), in 9% in those without a history of neurologic involvement (group III) and 0.9% in non-SLE controls, Although reactive with neurons, these antibodies were non-organ specific since they reacted with cells of non-nervous origin. The incidence and titer of antibodies to DNA and DNA-protein were however the same in the three groups of SLE patients suggesting that the high incidence of anti-cytoplasmic antibodies in group I may be specifically related to neuropsychiatric involvement rather than an expression of increased serologic reactivity of acutely ill lupus patients.