Opioids differ in their capacity to cause release of histamine. The effects of increasing concentrations of three opioids (morphine, buprenorphine, and fentanyl) were studied on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2 [PGD2] and peptide-leukotriene C4 [LTC4]) chemical mediators from human peripheral blood basophils and mast cells isolated from skin tissues or lung parenchyma. Basophils released < 5% of their histamine content and did not synthesize significant amounts of LTC4 when incubated with any of the opioids. Mast cells showed markedly different responses to the three opioids. Morphine (10(-5)-3 x 10(-4) M), in a concentration-dependent manner, induced histamine and tryptase release from skin but not from lung mast cells, up to a maximum of 18.2 +/- 1.9% and 13.0 +/- 4.1 micrograms/10(7) cells, respectively. Morphine did not induce de novo synthesis of PGD2 from skin mast cells. Buprenorphine (10(-6)-10(-4) M), in a concentration-dependent manner, caused histamine and tryptase release from lung but not from skin mast cells, to a maximum of 47.6 +/- 7.2% and 35.1 +/- 13.6 micrograms/10(7) cells, respectively. Buprenorphine also induced de novo synthesis of PGD2 and LTC4 from lung mast cells. Fentanyl (10(-5)-10(-3) M) did not induce histamine and tryptase release or the de novo synthesis of PGD2 or LTC4 from any mast cells. Histamine release caused by buprenorphine from lung mast cells was slow (t1/2 = 11.2 +/- 3.6 min) compared with that induced by morphine from skin mast cells (t1/2 < 1 min, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)