Random urine protein to creatinine ratio is a widely used index of the 24-h urine protein excretion, despite significant variability in creatinine excretion, depending on the severity and type of glomerular disease. To avoid this problem, the ratio of protein to osmolality (p/os) for the first morning urine specimen during a 24-h urine collection was compared to the 24-h urine protein excretion in 85 proteinuric patients, mean age 12 years (range 2-18 years), and in 62 normal subjects, mean age 10 1/2 years (range 2-17 years). In the normal group, the mean 24-h urine protein excretion was 81 mg (range 45-98 mg) and the mean urine p/os ratio (mg/mOsm) was 0.08 (range 0.06-0.11). The mean 24-h urine protein excretion in the patient group was 1.8 g (range 222 mg-7.6 g), and the mean urine p/os (mg/mOsm) was 2.1 (range 0.82-3.7). An excellent correlation was found between the collection of timed urine protein excretion and the random urine p/os ratio for all controls and proteinuric patients (r=0.92, P<0.01). A random urine p/os ratio equal to or greater than 0.15 indicated the presence of abnormal proteinuria. A urinary p/os ratio above 1.1 was considered to represent “nephrotic range” proteinuria (>1.0 g/m2/day). It was concluded that measurement of urine p/os ratio on the first morning urine sample is a simple and accurate quantitative assessment of protein excretion and could replace the 24-h determination of proteinuria.