In previous work (D.A. Vessey and T.D. Boyer, 1986, Biochem. Pharmacol., 35, 289-295) the activity of glutathione S-transferase form YcYc from rat liver was found to be stimulated by the herbicide 2,4,5-T. We have extended that work and examined the effect of over 40 structural analogs on the activity of YcYc. Over half of these compounds stimulated by 10 to 232% when added to assays at a concentration of 1 mM. The best activators all contained the "2,4,5-trichlorophenyl-" structure. While 2,4,5-T gave the greatest activation at 1 mM (2.3-fold), 2,4,5-trichlorobenzene sulfonate gave the greatest maximum activation (6.0-fold). Compounds that had no effect on activity did not affect activation by 2,4,5-T suggesting that they have a poor affinity for the enzyme. Two of the analogs tested (chloramine-T and 6-hydroxydopamine) proved to be good inhibitors and ethacrynic acid was an extremely potent inhibitor. Indomethacin activated at low concentrations but inhibited above 2 mM. Activations were greater at low temperature (5 degrees C) and decreased with increasing temperature. The extent of activation was largely unaffected by the concentration of either substrate. Examination of the organic peroxidase activity of the enzyme revealed inhibition by 2,4,5-T and 2,4-D rather than activation.