The potential for a pharmacokinetic (PK) drug-drug interaction between modafinil and methylphenidate, each at steady state, was investigated in an open-label, randomized, single-period study in 32 healthy male and female volunteers. All subjects received modafinil once daily orally for 28 days (200 mg on Days 1-7 and 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received 20 mg of methylphenidate orally 8 hours after their modafinil dose. PK profiles of modafinil were obtained on Days 21 and 28 and compared between the two groups. There were no statistically significant differences between the treatment groups in the mean changes in PK parameters for modafinil. Parameters for its metabolites were also similar between the groups, and all treatments were well tolerated. The results indicate that administration of low-dose methylphenidate 8 hours after treatment with modafinil does not appear to alter the steady-state pharmacokinetics of modafinil in healthy volunteers.