We describe 16 patients with Parkinson's disease seen during a 6-month period because of aggravation related to the recent introduction of a levodopa/carbidopa controlled-release (CR) preparation, either in combination with or substituting for the standard levodopa preparations. Disease duration was longer than 5 years (mean 8.4 +/- 5.9 years) in most cases at the time the CR preparation was introduced, and the patients were suffering from either severe late levodopa syndrome or progression in disability. For 9 out of 14 patients the CR formula had replaced the older preparation overnight. Though patients often accumulated multiple side-effects, we were able to identify 3 subgroups based on the main problem developing after the CR preparation had been introduced: a) apparent acceleration of the course of disease in patients in advanced stages, even if their response to treatment was otherwise stable (n = 4); b) subacute onset or aggravation of dyskinesias or painful "off"-period dystonia that often prompted reevaluation of the patient (n = 4); c) deterioration of akinetic "off" periods in patients already experiencing response fluctuations (n = 5) or appearance of dose failures in patients who had so far been enjoying stable responses (n = 3). These problems appeared in spite of a significant increase (p = 0.046) in total levodopa daily dose even though there were no differences (p = 0.685) in dose frequency between the CR preparation and standard levodopa.(ABSTRACT TRUNCATED AT 250 WORDS)