The effect of the dosage of methotrexate (MTX) on pharmacokinetic parameters in renal, hepatic and hematological functions were investigated. Twenty osteosarcoma patients (age: 13-53 years) received MTX infusions (dosage: 3.3-11.2g/m²) for 6 hrs. The serum MTX concentrations at 6h, 12h and 24h increased almost proportionally with the infused dose. The total serum MTX clearance and half-lives were almost constant in all the dosing ranges examined.<BR>To evaluate the relationship between the dosage and laboratory values, the patients were divided into three groups based on the MTX dosage and consisting of: low-dose (dosage: 3.3-5.2g/m²), middle-dose (dosage: 5.4-8.3g/m²), and high-dose (dosage: 9.0-11.2g/m²) groups. There was no significant difference between the renal and hematological functions before MTX infusion. In the high-dose group, significantly increased GOT and GPT values were observed on days 2 and 7, which indicate a decreased in hepatic function.<BR>In spite of the linear pharmacokinetics of MIX, a high-dose may cause remarkably nonlinear increased GOT and GPT values compared to those with low-and middle-doses.<BR>To avoid a severe adverse reaction of MTX therapy in the high-dosage group, careful monitoring of both the serum concentration of MTX and the liver functions is considered to be important after infusion.