Experimental evidence is given that the hallucinogen harmaline (HME) behaves as an inhibitor of the (Na+§ system, specifically in the Na +- dependent phosphorylation reaction. HME at 0.3 to 3 mM inhibited several membrane ATPase preparations such as those from human erythrocytes, rat brain and squid retinal axons. The same concentration blocked Na+ outflow from squid giant axons. The behavior of several harmane derivatives such as harmine, harmalol and harmaline demonstrated that certain groups influenced the concentration for 50 % inhibition of the ATPase system. The following evidence demonstrated that HME blocked the formation of the phosphorylated intermediate by competition with Na ions in the (Na++K+)- ATPase reaction in rat brain. (1) The HME effect on the overall (Na++ K+)-ATPase reaction showed a fully competitive inhibition with respect to Na ion concentration. (2) The inhibition of the Na+-stimulated phosphorylation by HME was fully competitive with respect to Na ions, with or without oligomycin present. (3) HME inhibited the effect of ADP on the phosphorylation reaction using 32p-ATP. (4) HME did not accelerate the rate of membrane dephosphorylation by means of 32p-ATP and cold ATP. From the behavior of HME as a competitive inhibitor at Na ion sites of the (Na + + K+)-ATPase reactions one may gain information about (a) The chemical nature of Na + sites which may be responsible for the selectivity of this cation, and (b) The sequence of Na + and ATP entrance into the Na+-dependent phosphorylation reaction. The experimental evidence supports the hypothesis that the entrance of Na+ into the enzyme system may precede the formation of the phosphorylated intermediate.