Rationale: Severe sialorrhea is a common, potentially stigmatizing and disabling side-effect of neuroleptic drugs such as clozapine. Sialorrhea also occurs in neurological disorders such as Parkinson's disease (PD). For neurological diseases, several studies have demonstrated botulinum toxin type B to be a safe and effective treatment. Objectives: To evaluate the treatment effects, tolerance, and duration of treatment-induced effects of botulinum toxin type B (Neurobloc®) in the context of neuroleptic-induced sialorrhea (group 1) or PD-associated drooling (group 2) in a double-blind, placebo-controlled trial. Methods: Nine patients (four from group 1; five from group 2) with severe sialorrhea received injections into the salivary glands with either botulinum toxin type B or placebo and were followed over 16 weeks. Results: We found large effect sizes for improvement of sialorrhea in patients treated with botulinum toxin type B, whereas the improvement of sialorrhea in those receiving placebo was only small. No patient reported any side effects. Reduction of sialorrhea lasted for 8 to 16 weeks after a single injection. Conclusions: Like for PD, botulinum toxin type B represents an effective and safe treatment for neuroleptic-induced sialorrhea with a treatment effect of 8 to 16 weeks.