1 The relation between plasma water phenytoin content and whole plasma phenytoin content in vivo was studied in 22 elderly patients (age range 62 to 87 years) and in 22 young patients (age range 18 to 33 years), all of whom were taking the drug for epilepsy. 2 The percentage of the drug existing unbound in plasma was slightly, but statistically significantly, higher in the elderly (12.8 +/- 1.8%) than in the young (11.1 +/- 2.5%). Reduced plasma albumin levels in the elderly (33.0 +/- 2.0 gl-1) as compared with the young (45.3 +/- 3.5 gl-1) probably contributed to the reduced protein binding in the older subjects.