The action of thiamine and a number of its analogs on tibialis twitch response to peroneal nerve stimulation, respiration, and arterial pressure, as well as their effect on the neuromuscular block produced by d-tubocurarine and decamethonium, were studied in anesthetized cats. It was found that thiamine, pyrithiamine, and pyrithiamine analogs in which there is a hydroxy group on the pyridinium ring caused a decrease in the twitch without initial potentiation, depressed respiration, and lowered arterial pressure. These compounds also antagonized both d-tubocurarine and decamethonium. On the other hand, methyl thiazolium iodide, methyl pyridinium iodide, and the analogs of thiamine and pyrithiamine in which there is no hydroxy group on the ring bearing the quarternary nitrogen, produced an increase in the twitch with muscular fasciculation, and with larger doses, a decrease in the twitch. Changes in respiratory movements generally paralleled those of the twitch. Arterial pressure was usually elevated. These compounds antagonized d-tubocurarine and potentiated decamethonium. The thiazolium fragment, at the dose level studied, increased the twitch only slightly. It also antagonized d-tubocurarine and potentiated decamethonium. The pyrimidine fragment seemed to have no effect on the twitch. It appears that the activity of thiamine and pyrithiamine on the neuromuscular junction is related to the quarternary nitrogen, the “pyrimidyl” coupling, and the presence of a hydroxy group on the onium-bearing ring. The antagonistic action of these compounds against df-tubocurarine and decamethonium also depends on the same structural components.