Trimethyllysine, a carnitine precursor, is a cation. This study was designed to determine whether dietary potassium and lysine concentration or oral lysine supplementation affects tissue carnitine and trimethyllysine concentration in rats. In Experiment 1, rats were fed a control diet, a low or high potassium diet, or a high lysine diet. In Experiment 2, rats were given by gavage a solution containing either L-proline (control) or L-lysine. In Experiment 1, rats fed the high lysine diet had significantly lower plasma total carnitine concentration than controls. Rats fed the high lysine diets had significantly higher concentrations of free trimethyllysine in skeletal muscle and plasma relative to control rats and rats fed the high potassium diet. Rats fed the low potassium diet had a similar increase in skeletal muscle free trimethyllysine. In Experiment 2, rats given lysine had significantly lower plasma total carnitine concentration, and significantly greater skeletal muscle and plasma trimethyllysine concentration relative to controls. We conclude that dietary potassium and lysine, and oral lysine, have a significant effect upon the distribution of carnitine and trimethyllysine in rats. The distributional changes caused by lysine, however, seem to be due to effects other than exchange of lysine for carnitine or trimethyllysine in tissues.