Although the etiology is unknown, a number of features of Henoch-Schönlein Purpura (HSP) suggest an immune pathogenesis. Using indirect immunofluorescence, we evaluated 19 patients with HSP for the presence of cold reacting antinuclear antibody (ANA). Eighteen of 19 patients demonstrated cold reacting ANA of the IgG class when human epithelial cells were utilized as substrate. The immunofluorescent pattern was speckled in all. One patient demonstrated ANA when tested at room temperature, while the remaining 18 were negative at room temperature. Cold reacting ANA persisted for periods of 6 months to 6 years in 10 patients, regardless of concomitant disease activity. None of the HSP patients demonstrated cold reacting ANA when mouse kidney sections were employed as substrate. Moreover, none demonstrated antibody to DNA or to extractable nuclear antigen. Sera from 20 normal adults, 10 normal children, and 7 children with juvenile rheumatoid arthritis were all negative when tested for cold reacting ANA. Cold incubation altered neither the ANA titer nor the immunofluorescent pattern in 5 patients with systemic lupus erythematosus. These results indicate that patients with HSP elaborate a cold reacting ANA which is substrate dependent.