The effects of an inhibitor of GABA synthesis, 3-mercaptopropionic acid (MP), and of the GABA antagonist bicuculline (BIC), on the direction and orientation sensitivity of visual cortical neurons were investigated using a computer-controlled stimulus presentation system. Intravenous administration of MP, which was usually more effective than if administered microelectrophoretically, induced a slight, but significant reduction in these properties of about half of the neurons tested. The effect of electrophoretic BIC was in the same direction but clearer than that of MP. In 71% of the simple cells, direction sensitivity was virtually lost during administration of BIC while orientation sensitivity was never completely eliminated in any neuron tested. Simultaneous administration of both drugs (MP systemically, BIC electrophoretically) caused more complete modification of the sensitivities than single administration of each. In four out of thirteen neurons tested, orientation sensitivity was completely abolished. The excitatory receptive fields slightly increased in size and became virtually round. The response magnitude to the optimal stimulus was increased by each drug along and by both. The present results further support the hypothesis that intracortical inhibition plays a major if not an exclusive role for the orientation and direction sensitivity of cortical cells.