Different ligands of both the "peripheral" and the "central" benzodiazepine receptors were tested for their ability to induce human monocyte chemotaxis. Only the ligands interacting with the "peripheral receptor" (diazepam and Ro 5-4864) were active, and their action was blocked by the specific antagonist PK 11-195, but not by the calcium channel blocker nimodipine. As expected, GABA did not stimulate chemotaxis and it did not modulate the chemotaxis induced by other benzodiazepine receptor ligands. The benzodiazepine inverse agonists FG 7142 and Ro 15-3505 were inactive on chemotaxis when given alone, but they enhanced the "peripheral" ligand induced chemotaxis. This effect was blocked by an agonist and an antagonist of the "central" receptor. These results suggest an interaction between the two different classes of benzodiazepine receptors on human monocytes.