In 5 out of 72 (7%) workers exposed to the asthma-inducing amine piperazine, specific IgE antibodies against a conjugate between human serum albumin and piperazine were demonstrated with RAST and RAST inhibition techniques. No specific antibodies were found in 64 nonexposed workers at the same plant, and in 60 healthy reference subjects. Eight out of the 72 (11%) exposed employees had unequivocal histories of piperazine-associated asthma, but only 4 of them had specific IgE antibodies against piperazine. However, there was a statistically significant association between specific antibodies and disease, as 4 out of 5 RAST-positive subjects were asthmatics, as compared with 4 out of the 67 RAST-negatives (p = 0.0003). The 4 RAST-positive asthmatics had been exposed to piperazine for between 6 and 168 months before their asthma started, as compared with induction times of less than a month for the 4 RAST-negatives. This discrepancy may reflect different pathogeneses for piperazine-associated asthma; either type-I allergy, pseudo-allergic reactivity or nonspecific irritative effect on the bronchi. The RAST-positive subjects did not differ from other employees as regards smoking habits but had significantly elevated levels of total serum IgE (p = 0.004).