A thalium chloride-resistant (TlClr) mutant strain and a sodium chloride-resistant (NaClr) mutant strain of the diazotrophic cyanobacterium Anabaena variabilis have been isolated by spontaneous and chemical mutagenesis by using TlCl, a potassium (K+) analog, and nitrosoguanidine (NTG), respectively. The TlClr mutant strain was found to be defective in K+ transport and showed resistance against 10 pm TlCl. However, it also showed sensitivity against NaCl (LD50, 50 mm). In contrast, neither wild-type A. variabilis nor its NaClr mutant strain could survive in the presence of 10 muM TlCl and died even at 1 mum TlCl. The TlClr mutant strain exhibited almost negligible K+ uptake, indicating the lack of a K+ uptake system. High K+ uptake was, however, observed in the NaClr mutant strain, reflecting the presence of an active K+ uptake system in this strain. DCMU, an inhibitor of PS 11, inhibited the K+ uptake in wild-type A. variabilis and its TlClr and NaClr mutant strains, suggesting that K+ uptake in these strains is an energy-dependent process and that energy is derived from photophosphorylation. This contention is further supported by the inhibition of K+ uptake under dark conditions. Furthermore, the inhibition of K+ uptake by KCN, DNP, and NaN3 also suggests the involvement of oxidative phosphorylation in the regulation of an active K+ uptake system. The whole-cell protein profile of wild-type A. variabilis and its TlClr and NaClr mutant strains growing in the presence of 50 mm KCl was made in the presence and absence of NaCl. Lack of transporter proteins in TlClr mutant strain suggests that these proteins are essentially required for the active transport and accumulation of K+ and make this strain NaCl sensitive. In contrast, strong expression of the transporter proteins in NaClr mutant strain and its weak expression in wild-type A. variabilis is responsible for their resistance and sensitivity to NaCl. respectively. Therefore, it appears that the increased salt tolerance of the NaClr Mutant strain was owing to increased K+ uptake and accumulation, whereas the salt sensitivity of the TlClr mutant strain was owing to the lack of K+ uptake and accumulation.