To investigate possible immune mechanisms responsible for levamisole-associated neutropenia we tested patients with bladder cancer on levamisole therapy. Autoimmune and complement-dependent granulocytotoxic antibodies were detected in 3 patients with levamisole-induced neutropenia. The granulocytopenia appeared to be causally related to the presence of autoantibodies in that pretreatment serum or serum obtained after the restoration of neutrophil counts showed diminished or no granulocytotoxic reactivity. In addition, granulocytotoxins were found in 6 out of 20 (30%) patients receiving levamisole compared to only 2 out of 28 (7.1%) patients on no levamisole or placebo (P less than 0.06). Hence, screening for granulocytotoxins may forewarn of neutropenia in patients receiving levamisole for a variety of clinical diseases.