Two methods employing lysosomal enzyme release and light scattering measurements have shown that Cephaloridine Stabilises rat kidney lysosomes in vitro against beta-Progesterone and lysolecithin, the two well known agents to labilise lysosomal membranes. Treatment of the isolated lysosomes suspended in 0.25 M-sucrose-EDTA (0.34 mM) pH 7.4 with cephaloridine (100mcM) at 37 degrees C for 10 min. and subsequent incubation of the mixture with progesterone (0.25mM) at the same temperature for varying periods of time up to 50 min. resulted in no significant changes from the normal values in the release of acid phosphatase activity obtained from the supernatant fraction after centrifugation of the incubated mixture at 33,000g. for 5 min. at 4 degrees C. When lysosomes were mixed with cephaloridine before treatment with progesterone or lysolecithin, and then subjected to light scattering measurements, lysosomal swelling was considerably decreased, indicating that cephaloridine could exert a stabilising effect on rat kidney lysosomal membrane and thereby limit the release of lysosomal acid hydrolases.