Concentrations of endogenous "true" creatinine in saliva and serum were measured in 6 normal subjects using a specific and sensitive high-performance liquid chromatographic method. There were marked intra- and intersubject variations in saliva levels during an 11-wk study. There were also large variations in the ratios of the saliva/serum creatinine level during the one-day study for all the subjects, the average highest intrasubject variation being 481% and the range being 128% to 816%. The average ratio of saliva/serum level was 0.0999 +/- 0.097 (CV = 97%); the highest saliva level was 1.5 mg%. Lower salivary levels were probably due to the extremely low lipid solubility of creatinine resulting in a relatively slower diffusion rate than of the transport of water into the saliva. Salivary monitoring of creatinine is concluded to be of little use in indicating its concentration in plasma or serum because, unlike many other substances it does not follow the pH-partition principle for saliva/plasma distribution.