The effect of 5'-deoxy-5'-methylthioadenosine (MTA) on the growth of culture murine lymphoid cells was examined. MTA inhibited the growth of murine lymphoid cell lines of both B- and T-cell origin in a reversible, nontoxic, and dose-dependent fashion. When measured 2 days after the addition of MTA to the cells, the concentration that inhibited proliferation by 50% for MTA was about 250 muM. Cells incubated in the presence of 0.5 mM MTA for 1, 2, or 3 days were able to recover from the inhibitory effect of the nucleoside and resumed growth. Six structural analogs of MTA were also found to inhibit cell growth. Five of these analogs served as alternative substrates for MTA phosphorylase, while one, the 7-deaza analog (5'-deoxy-5'-methylthiotubercidin), was not a substrate for the phosphorylase but was a potent inhibitor of enzyme activity. Inhibition of growth by 5'-deoxy-5'-methylthiotubercidin was dose dependent (the concentration that inhibited proliferation by 50% approximately or equal to 10 muM) and at 50 muM was reversible and nontoxic.