We present an analysis of the clinical significance of creatinine concentrations less than or equal to 4 mg/L (35 mumol/L) in serum as measured by a specific enzymatic method. In an unselected hospital patient population, 4% of whom had serum creatinine concentrations this low, a value of 5 mg/L (44 mumol/L) or higher was obtained on repeat analysis for a third of these patients, but the remaining two-thirds had persistently low values. Associated clinical conditions included low body mass, pregnancy, insulin-dependent diabetes mellitus, and total immobilization, but 12% of the patients, all female, had no obvious cause for the persistently low creatinine concentration. We conclude that low concentrations of creatinine in serum have no profound clinical significance.