Occupational exposure to formaldehyde (HCHO) has been implicated in development of both dermal hypersensitivity and pulmonary hypersensitivity. The purpose of this study was to assess the route of exposure most likely to cause sensitization in animals and the potency of formaldehyde as a sensitizing chemical. Three routes of exposure were utilized: inhalation, dermal, and injection (with Freund's complete adjuvant). For inhalation exposure, groups were exposed to 6 ppm (Group I) or 10 ppm HCHO (Group II) for 6 hr/day or 8 hr/day (Group III) on 5 consecutive days. Animals were evaluated for skin sensitivity, production of anti-HCHO antibody, and respiratory sensitivity (both immediate- and delayed-onset) to HCHO. Of the animals receiving inhalation exposure, two of four animals in Group III displayed dermal sensitivity. No antibodies or pulmonary sensitivity were detected in any animals in any of these groups. Animals exposed to HCHO by injection displayed extensive dermal reactions when skin tested. In addition, two of four animals in this group developed antibodies to HCHO in low titer. No pulmonary sensitivity was detected. Animals exposed to HCHO by dermal contact developed neither pulmonary sensitivity nor antibodies to HCHO. However, all of these animals developed skin sensitivity. The severity of the contact sensitivity response, as well as the percentage of animals sensitized, increased with exposure dose. These results indicated that HCHO was a skin sensitizer in the guinea pig without causing detectable respiratory hypersensitivity.