The physiopathology of levodopa-induced dyskinesias (LIDs) is unclear. Presynaptic pharmacokinetic and postsynaptic pharmacodynamic mechanisms may be involved. We have analyzed several clinical and pharmacological parameters, as well as the status of the presynaptic dopamine nigrostriatal pathway by using DaTSCAN, in 14 patients with Parkinson disease who developed early and severe LID despite using low doses of levodopa and 10 patients without this complication despite the use of high levodopa doses. Patients were matched for age at onset, duration, and severity of Parkinson disease. Statistically significant differences were observed only in the duration of LID during the levodopa challenge. However, clear differences were also observed in weight and sex distribution (women with low weight predominate in the group with dyskinesia), severity and duration of LID, and total levodopa dosage. The pattern of response to levodopa and the uptake of (123I)N-w-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane were similar in both groups. These results indicate that the development of LID needs additional contributions beyond nigrostriatal denervation. Factors related to sex and body weight could play an important role. However, these findings should be considered cautiously because of the limited statistical power of the study.