The subclass distribution of antibodies against alpha toxin from Staphylococcus aureus in man was investigated. Antibodies were restricted to IgG1, IgA1, and IgG4 and appeared to develop sequentially. These data suggest a distinct pattern of class and subclass switches in response to protein antigens. However, studies in immunodeficient (class- or subclass-deficient) donors show that the proposed patterns is not obligatory.