Calf thymus nucleosomes containing H1 were treated with dichlorodiammineplatinum (DDP) at low binding ratios (r = 0.05-0.15). Change in the electrophoretic mobility of the extracted nucleosomal DNA was observed following treatment with cis-DDP and little change with trans-DDP. There was a decrease in the electrophoretic mobility of the nucleosomal DNA as well as obliteration of the nucleosomal repeat distance. The fluorescence intensity of terbium binding to the extracted DNA showed minimal change following drug treatment. However, the thermal melting behavior of the nucleosomal DNA was altered to a greater extent following cis-DDP treatment at 280 rather than 260 nm and a destabilization of the DNA helix was observed. These data suggest that in the whole nucleosome, cis-DDP produces greater structural effects on the packaged DNA than trans-DDP, although similar amounts of drug are bound with both isomers.