The effects of age and concomitant treatment on plasma lamotrigine (LTG) concentration/dose (C/D) ratios were retrospectively evaluated on 482 consecutive routine LTG determinations from 106 chronically-treated patients with epilepsy (40 children and adolescents aged younger than 16 years, and 66 adults aged 17 to 62 years). A linear dose/level relationship was observed in individual patients but not in the cumulative analysis, which failed to show any correlation between the administered LTG dose and plasma concentrations. In the adult group, there were no correlations between the administered LTG dose and plasma concentrations. Associated antiepileptic therapy affected the LTG concentration/dose ratio, which was significantly higher in the patients receiving valproic acid (3.4 +/- 2.0, n = 23) and significantly lower in those treated with enzyme-inducing antiepileptic drugs (0.6 +/- 0.5, n = 57) than in the patients receiving valproic acid in combination with enzyme-inducing antiepileptic drugs, ethosuximide, vigabatrin, or clobazam (1.9 +/- 1.6, n = 26). The LTG C/D ratios significantly increased with increasing plasma valproic acid concentrations, and significantly decreased with increasing phenytoin concentrations. The effect of enzyme-inducing antiepileptic drugs increased with the number of associated drugs. A clear age effect was demonstrated in the homogeneously treated subgroups, in all of which adults had higher C/D ratios than children.