Toxin- (T) from the Brazilian scorpion Tityus serrulatus venom caused a concentration- and time-dependent increase in the release of norepinephrine and epinephrine from bovine adrenal medullary chromaffin cells. T was ~200-fold more potent than veratridine judged from EC₅₀ values, although the maximal secretory efficacy of veratridine was 10-fold greater than that of T (1.2 vs. 12 µg/ml of catecholamine release). The combination of both toxins produced a synergistic effect that was particularly drastic at 5 mM extracellular Ca²⁺ concentration ([Ca²⁺]_o), when 30 µM veratridine plus 0.45 µM T were used. T (0.45 µM) doubled the basal uptake of ⁴⁵Ca²⁺, whereas veratridine (100 µM) tripled it. Again, a drastic synergism in enhancing Ca²⁺ entry was seen when T and veratridine were combined; this was particularly pronounced at 5 mM [Ca²⁺]_o. Veratridine induced oscillations of cytosolic Ca²⁺ concentration ([Ca²⁺]_i) in single fura 2-loaded cells without elevation of basal levels. In contrast, T elevated basal [Ca²⁺]_i levels, causing only small oscillations. When added together, T and veratridine elevated the basal levels of [Ca²⁺]_i without causing large oscillations. T shifted the current-voltage (I-V) curve for Na⁺ channel current to the left. The combination of T with veratridine increased the shift of the I-V curve to the left, resulting in a greater recruitment of Na⁺ channels at more hyperpolarizing potentials. This led to enhanced and more rapid accumulation of Na⁺ in the cell, causing cell depolarization, the opening of voltage-dependent Ca²⁺ channels, and Ca²⁺ entry and secretion.