This study demonstrated that the administration of a spherulin skin test to subjects whose skin-test reactions were either positive or negative, at the dose used (Usual Test Strength), did not elicit an antibody response to antigens of Coccidioides immitis or Histoplasma capsulatum, as determined by standard serologic methods. Of 32 subjects, one developed a seroconversion by the latex agglutination test. The data suggested that spherulin can be used clinically as a diagnostic reagent without affecting the serologic reactions, which are of both prognostic and diagnostic value.