Thiazolidine carboxylic acid (TCA) is a natural liver metabolite whose Mg-salt increased lifespan of flies and mice (Miquel and Economos, 1979, Exp. Geront. 14: 279). We studied the physiological and cellular fine structural effects of various concentrations of TCA in the food of male Drosophila. Flies on 0.3% TCA at 27 degrees C had a reduced oxygen consumption rate (about 20% less than controls) at 3 wks of age while their mating capacity and speed of mating were preserved; the flies lived in various experiments 20-30% longer than controls. Apparently TCA improved the metabolic efficiency of the flies (possibly from less "waste" of energy due to improved mitochondrial coupling). However, flies on 0.9% TCA had a reduced mating capacity and lifespan (:toxicity) while at 0.1% TCA was ineffective. A similar dose-response relationship was found in young flies treated with TCA for 1 week and then deprived of food and water, a procedure found to induce accelerated physiological aging. TCA at the 0.3% and 0.6% level reduced the speed of development and the size of the enclosed flies. Electron microscopic investigation of wing muscle showed that 0.3% TCA had a protective effect on cellular fine structure. Though in starved controls (40% survivors after 24 hours of starvation) there was a total absence of glycogen granules, and a striking shrinkage and densification of mitochondria, TCA to a large extent protected muscle cells from these effects of starvation.