A patient is presented with clinical and histologic evidence of subcorneal pustular dermatosis. In other patients sulfapyridine and the sulfones have proved to be effective therapeutic agents. The case presented failed to respond favorably to either a sulfone (Diasone), sulfisoxazole (Gantrisin), or tetracycline (Achromycin), but responded specifically to sulfapyridine. Tripelennamine (Pyribenzamine) seemed to act synergistically with sulfapyridine and permitted reduction in the therapeutic dosage of sulfapyridine. Pyridoxine alone was ineffective. The possible role of the pyridine ring is speculated on as a therapeutic factor. Future trial with both of these compounds (tripelennamine and pyridoxine) must be performed before any valid conclusions can be properly drawn.