Acute neuritis and persistent pain are the most significant clinical manifestations of herpes zoster and are end points for clinical trials therapy. In an acyclovir and prednisone study, patients were categorized according to pain severity and number of lesions at presentation. Risk categories were defined according to the magnitude of risk ratios (RRs) and a comparison of Kaplan-Meier survival estimates. For acute neuritis and zoster- associated pain, RRs defined rate of resolution. Patients who presented with severe or incapacitating pain and a large number of lesions were less likely to achieve resolution of both acute neuritis and zoster-associated pain CRR, 18.0; 95% confidence interval [CI], 6.6-48.6, and RR, 5.3; 95% CI, 4.2-17.2, respectively). These analyses identify the subgroups of patients for whom aggressive interventions are most strongly indicated.