Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) show clinical and epidemiological differences not accounted for by different ultraviolet radiation exposure. We have studied experimentally induced contact sensitivity to dinitrochlorobenzene by measuring increases in skin-fold thickness. Patients (n = 37) with squamous tumours had impaired responses compared with controls (33) and patients with BCCs (31) (mean increase 4.5 vs 7.8 and 8.6 mm, respectively; p = 0.002). This diminished immunological response may be causally related to the development of SCC. Because glutathione S-transferase (GST) metabolises dinitrochlorobenzene and polymorphisms of GST are associated with multiple skin tumours, variations in GST may underlie these differences.