The pharmacokinetics of single and co-administered didanosine and stavudine were evaluated in 10 HIV-seropositive subjects in an open, within subject design in which each subject received each of three treatments. Single doses of didanosine 100 mg were alternated randomly with single doses of stavudine 40 mg on days 1 and 2. Beginning on day 3, subjects received the same doses of both drugs simultaneously every 12 h for nine doses. Serial blood and urine samples were obtained on single dose days 1 and 2, first simultaneous dose day 3, and last simultaneous dose day 7. The average maximum plasma concentrations of didanosine and stavudine before and after simultaneous administration were 422 +/- 184 (s.d.) ng ml-1 and 603 +/- 160 (s.d.) ng ml-1, and 419 +/- 153 (s.d.) ng ml-1 and 726 +/- 188 (s.d.) ng ml-1, respectively. Didanosine and stavudine AUC values before and after simultaneous administration were 615 +/- 170 (s.d.) ng ml-1 h and 1246 +/- 230 (s.d.) ng ml-1 h, 637 +/- 155 (s.d.) ng ml-1 h and 1326 +/- 267 (s.d.) ng ml-1 h, respectively. No significant changes in maximum plasma concentration, AUC elimination half-life, or renal clearance of didanosine and stavudine were observed when the drugs were administered simultaneously. Co-administration of didanosine 100 mg and stavudine 40 mg is well tolerated and the drugs do not interact pharmacokinetically.