Whole-cell patch-clamp recordings were made from macrophages derived from human monocytes that had been cultured for 5-7 days. The P2X agonists ATP (100 microM) and 2',3'-(4-benzoyl)-benzoyl ATP (BzATP, 100 microM) induced inward currents. A second application of the agonists was characterized by strong desensitisation of the maximum current. Pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a non-specific P2X antagonist, and 1-( N, O- bis[5-isoquinolinesulphonyl]- N-methyl- L-tyrosyl)-4-phenylpiperazine (KN62), a potent P2X(7) antagonist at the human receptor, both reduced the ATP-induced inward current. KN62 also inhibited the BzATP-induced current. The P2X(7) antagonist Coomassie Brilliant Blue G (BBG), believed to be potent at the human but even more so potent at the rat receptor, did not reduce the BzATP-induced inward current significantly. These results indicate that the native P2X(7) receptor subtype is expressed in human macrophages and that this receptor subtype is involved in the ATP-mediated inward current. Our experiments suggest that other P2X receptors also appear to be involved in the ATP-mediated current in human monocyte-derived macrophages.