Herpes simplex virus-2, the most common cause of genital ulcer disease (GUD) globally, is a cofactor in human immunodeficiency virus type-1 (HIV-1) acquisition and transmission. Current World Health Organization guidelines for sexually transmitted infections recommend acyclovir as first-line syndromic treatment of GUD in countries with high herpes simplex virus-2 prevalence (> or =30%). To assess the extent of adoption of acyclovir as syndromic treatment for GUD, and describe procurement, distribution, and cost of acyclovir in the public and private sectors of 8 sub-Saharan African countries. We conducted standardized interviews with Ministry of Health (MoH) officials, pharmacists, and other pharmacy workers based in the public and private sectors. Interviews were conducted in Botswana, Kenya, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. Price comparisons were conducted using the 2007 median international reference price (IRP) for acyclovir. Of the 8 African countries, 4 surveyed had adopted acyclovir as first-line syndromic GUD treatment in both their essential medical lists and sexually transmitted infection guidelines. Country-specific acquisition prices for acyclovir 200 mg were comparable to the median IRP and ranged from 0.74 to 1.95 times the median IRP. The median retail cost of acyclovir in the private sector ranged from 5.85 to 9.76 times the median IRP. Public health facilities faced cost and regulatory barriers that impeded the requisitioning of acyclovir from the central medical stores. Systems for drug procurement, distribution, and access in sub-Saharan African countries need strengthening for a GUD treatment policy using acyclovir to be effective.