Objective. To study antibodies directed against ribosomal P proteins, a sensitive and specific marker of depression and psychosis in systemic lupus erythematosus (SLE), in pediatric patients with SLE. Methods. One hundred six serum samples were obtained from 79 patients with SLE. Sixty age- and sex- matched control sera were obtained, and 12 samples were obtained from children with primary psychosis. Antibodies to recombinant ribosomal P (rRP) protein were detected using a standard enzyme-linked immunosorbent assay. Results. All 12 children with non-SLE-associated psychosis had normal levels of anti-rRP antibodies. Elevated levels of anti-rRP were found in 11 of 64 pediatric SLE patients without a history of psychosis (17%). In the group of 13 SLE patients with psychosis, 5 (38%) had increased anti-rRP antibody levels during the time of acute psychosis, and which significantly decreased during remission. In addition, most of the SLE patients without a history of psychosis had a good correlation between anti-rRP antibody levels and disease activity. The patients with psychosis had significantly less renal involvement than the patients without a history of psychosis. This apparent protection from renal disease was not related to the presence or absence of either antiribosomal P or anti-DNA antibodies. Conclusion. Elevated serum levels of antibodies to ribosomal P protein can distinguish SLE-associated psychosis from primary psychosis of childhood. In SLE, elevated antiribosomal P antibody levels were not specific for psychosis. Serial assays were useful for monitoring the disease activity.