Many health plans have instituted more cost sharing to discourage use of more expensive pharmaceuticals and to reduce drug spending. To determine how changes in cost sharing affect use of the most commonly used drug classes among the privately insured and the chronically ill. Retrospective US study conducted from 1997 to 2000, examining linked pharmacy claims data with health plan benefit designs from 30 employers and 52 health plans. Participants were 528,969 privately insured beneficiaries aged 18 to 64 years and enrolled from 1 to 4 years (960,791 person-years). Relative change in drug days supplied (per member, per year) when co-payments doubled in a prototypical drug benefit plan. Doubling co-payments was associated with reductions in use of 8 therapeutic classes. The largest decreases occurred for nonsteroidal anti-inflammatory drugs (NSAIDs) (45%) and antihistamines (44%). Reductions in overall days supplied of antihyperlipidemics (34%), antiulcerants (33%), antiasthmatics (32%), antihypertensives (26%), antidepressants (26%), and antidiabetics (25%) were also observed. Among patients diagnosed as having a chronic illness and receiving ongoing care, use was less responsive to co-payment changes. Use of antidepressants by depressed patients declined by 8%; use of antihypertensives by hypertensive patients decreased by 10%. Larger reductions were observed for arthritis patients taking NSAIDs (27%) and allergy patients taking antihistamines (31%). Patients with diabetes reduced their use of antidiabetes drugs by 23%. The use of medications such as antihistamines and NSAIDs, which are taken intermittently to treat symptoms, was sensitive to co-payment changes. Other medications--antihypertensive, antiasthmatic, antidepressant, antihyperlipidemic, antiulcerant, and antidiabetic agents--also demonstrated significant price responsiveness. The reduction in use of medications for individuals in ongoing care was more modest. Still, significant increases in co-payments raise concern about adverse health consequences because of the large price effects, especially among diabetic patients.