Methotrexate (MTX) is used in the medical treatment of unruptured ectopic pregnancy. This drug is administered by intramuscular (IM) or intrasaccular (IS) injection under sonographic control. No data are available concerning the pharmacokinetics of MTX in this new indication. This study compares the two administration routes in 12 patients (21 to 37 years) taken as their own control and presenting with ectopic pregnancy (51 +/- 12 days of amenorrhea). Our aim was to compare the pharmacokinetic profile of MTX for each route to facilitate its use in the future. The initial level of hCG was 4.474 +/- 4.184 mIU/ml. Each patient firstly received 1 mg/kg of MTX intrasaccularly under vaginal sonography. The same dose was injected intramuscularly 48 hours later. The pharmacokinetic profiles of MTX after IS and IM administrations were determined after both injections during 48 hours. MTX serum levels were measured by Fluorescence Polarization Immuno Assay. Data were analyzed by model independent methods and compared by a Wilcoxon T test (p 0.01 was considered as significant). All the unruptured ectopic pregnancy were cured and the hCG serum levels were normalized (10 mIU/ml) in 37 +/- 18 days. After IM administration, AUC0-infinity is significantly (p 0.01) increased i.e., 15.1 +/- 4.1 mumol.h/l versus 11.2 +/- 4.8 after IS injection. T1/2 lambda z and MRT remained unchanged whatever the route is i.e., 11.3 +/- 4.9 h and 8.6 +/- 3.9 h (IS) versus 12.1 +/- 5.9 h and 7.3 +/- 1.8 h (IM). The decrement of AUC0-infinity 8 determined after IS injection might be the consequence of the capture of the MTX by the trophoblastic cells (target cells).(ABSTRACT TRUNCATED AT 250 WORDS)