The effects of podophyllotoxin (PPT), etoposide (VP16), and teniposide (VM26) on the growth of Tetrahy mena thermophila BF.sub.5 (T.t.BF.sub.5) was investigated by the TAM AIR isothermal microcalorimetric system. The extent and duration of toxic effects on T.t.BF.sub.5 metabolism were evalu ated by studying the growth rate constant (k), inhibitory ratio (I), maximum heat-output power (P.sub.max), peak time of maxi mum heat-output power (t.sub.p), and total heat production (Q.sub.t). Experimental results showed that the value of t.sub.p increased and the value of k and P.sub.max decreased with the increasing com pound concentrations. Furthermore, the growth rate constant k was linear with compound concentration. The corresponding I was obtained from different k values. According to the IC.sub.10 (the concentration of inhibitor when the inhibitory ratio is 10%), the relative toxicity of the three compounds was PPT (IC10 = 49.6 µ mL.sup.-1) > VP16 (IC.sub.10 = 117.5 µg mL.sup.-1) > VM26 (IC.sub.10 = 359.1 µg mL.sup.-1). The preliminary investigation of structure-activity relationships showed that the thienyl group was likely responsible for reducing the toxicity of the compounds. Keywords Microcalorimetry * Podophyllotoxin * Etoposide * Teniposide * Tetrahymena thermophila BF.sub.5