The role of isoniazid prophylaxis in low-risk patients with positive Mantoux skin tests has recently been questioned. In general, recent research has focused on the risk/benefit ratio. We, therefore, decided to extend these data and apply a cost-effectiveness analysis of the routine use of isoniazid prophylaxis from a societal perspective. Costs per case prevented were calculated for a 20-, 50-, and 70-yr-old low-risk patient who had a positive Mantoux test with base, high, and low costings. Rates were also calculated based on the use of direct costs alone and direct and indirect costs combined. Costs varied from Canadian $8,586.00 in a 20-yr-old patient to $40,102.00 in a 70-yr-old patient per case prevented based on direct costs with costs ranging from $3,236.00 to $11,320.00 with both direct and indirect costs included. These costs could be considered reasonable from a societal perspective but do not address the issue of any increased life expectancy resulting from chemoprophylaxis.