1. To identify some of the neurotransmitters involved in the processing of visual motion information the pharmacology of transmitter receptors on motion-sensitive visual interneurons (VS and HS cells) was investigated in an in vitro preparation of the blowfly (Calliphora erythrocephala) brain. Cholinergic and GABAergic drugs were applied in the bath and iontophoretically while recording intracellularly from HS and VS cells. 2. Bath-applied carbachol (10 and 100 microM) leads to a depolarization in HS and VS cells. One micromolar nicotine also has a depolarizing effect. Both agonists are effective in 0 Ca2+/high Mg(2+)-saline, too, which isolates the cells synaptically. The muscarinic agonists pilocarpine and oxotremorine have no effects on the membrane potential. 3. Iontophoretic application of acetylcholine, carbachol, and nicotine depolarizes VS and HS cells. The iontophoretic carbachol response is antagonized by alpha-bungarotoxin (EC50 = 0.19 microM), mecamylamine (EC50 = 0.32 microM), d-tubocurarine (EC50 = 9.5 microM), and bicuculline but not by decamethonium and scopolamine. 4. Bath application of muscimol strongly hyperpolarizes VS cells in normal fly saline. The gamma-aminobutyric acid-C (GABAC)-receptor agonist cis-4-aminocrotonic acid (CACA) has no effects. The hyperpolarizing response to iontophoretic applied muscimol is present in 0 Ca2+/high Mg2+ saline as well as in Co(2+)-containing saline. The muscimol response is reduced in low chloride saline and thus chloride sensitive. The muscimol response is blocked by picrotoxinin (EC50 = 3.4 microM) but not by the GABAA receptor antagonist bicuculline. 5. Taken together the primary responses of the lobula plate tangential cells appear to be nicotinic cholinergic and GABAergic. 6. The pharmacology of natural synaptic input to VS cells was investigated by extracellular electrical stimulation of the medulla. Such evoked excitatory postsynaptic potentials (EPSPs) are blocked reversibly in 0 Ca2+/high Mg2+ saline. The nicotinic antagonists mecamylamine (1 microM) and d-tubocurarine (50-100 microM) abolish or diminish the EPSPs, respectively. 7. The pharmacological data are incorporated into a semicellular model of a visual motion detector favoring a role of lobula plate tangential cells in certain steps of visual motion processing. Cholinergic and GABAergic inputs are an ideal cellular implementation of a linear subtraction of the signals arising from local motion-sensitive elements with opposite preferred direction. Such a mechanism enhances direction-selectivity and, together with dendritic integration, increases the sensitivity of the tangential cells for wide-field motion.