Beta-Bungarotoxin, crotoxin and notexin were treated extensively with p-bromophenacyl bromide in order to modify the histidine group of the active site and to greatly decrease the phospholipase A2(PLA) catalytic activity. They were studied for their residual presynaptic effects on the mouse isolated phrenic nerve-diaphragm and chick biventer cervicis muscle preparations. The modified toxins still had 1.7-5.2% PLA activity, which was inhibited by Sr2+, as is the enzyme activity of the native toxins. The neuromuscular blocking activity of these modified toxins, which was reduced 30-60 fold in the mouse diaphragm, was due to a presynaptic effect, as judged from the unchanged amplitude of m.e.p.p.s in the blocked preparations. In contrast to the native toxins, however, the presynaptic effect of modified beta-bungarotoxin and notexin was neither antagonized by Sr2+ nor accelerated by increasing the rate of nerve stimulation, indicating that the presynaptic effects of the modified beta-bungarotoxin and notexin are not likely to be due to their PLA enzyme activity. The modified toxins retained a much greater fraction of their early presynaptic effects in comparison to their enzymatic and neuromuscular blocking activities, although the time-course of the early effects was delayed. The results indicate that the modified neurotoxins per se have their own presynaptic effects, which are unrelated to the PLA enzyme activities.