Diisocyanates, as a chemical class, are recognized for their ability to cause respiratory and dermal sensitization. By contrast, monofunctional isocyanates have not been associated with cases of clinical sensitization. We investigated the immunologic activity of phenyl isocyanate (PI), an aromatic monoisocyanate, which is a trace constituent in commercial diphenyl methane diisocyanate (MDI) products, since it is has been reported to cause an "asthma-like' syndrome in rats. The potency of PI as a contact sensitizer was assessed using the mouse ear swelling test. PI was found to be the most potent isocyanate tested yielding an SD50 (dose predicted to sensitize 50% of the mice) of 0.04 mumol/kg, compared with SD50 values of 0.5, 2.1, and 30.4 mumol/kg, for the diisocyanate sensitizers hexamethylene diisocyanate, MDI, and toluene diisocyanate (TDI), respectively. When tested for ability to stimulate humoral immune responses, antibody titers to PI were more than ten-fold greater than those induced by TDI. The mean hapten-specific IgG antibody titer to PI was 1.4 x 10(4), compared with 1.3 x 10(3) for TDI. The anti-PI IgG1 anaphylactic antibody titer (1.2 x 10(4) was significantly greater than the anti-TDI IgG1 titer of 6.4 x 10(2). Hapten-specific IgE was not detected to either isocyanate. These results indicate that phenyl isocyanate is a potent inducer of both cellular and humoral immune responses. This activity may be a significant contribution to the sensitization potential of commercial products in which it is a trace contaminant.