Effect of route of administration and timing on the ability to control GVHD. (A): Mice were given transplants as described in Materials and methods of 1 × 107 bone marrow cells plus 2 × 106 TK+TC (TK) or 2 × 106 TK+TC followed by the intraperitoneal administration of GCV daily for 7 days starting on days 4 (○), 7 (□), 10 (Δ), or 13 (+). The survival time of all treated groups was significantly longer than that of the untreated group (p = 0.005 [day 4], p = 0.00002 [day 7], p < 0.00001 [day 10], or p = 0.005 [day 13]), even though some mice in the day 13 group had died of GVHD before the initiation of GCV. (B): Mice were given transplants as described in Materials and methods of 1 × 107 bone marrow cells plus 2 × 106 TK+TC (▲) or TK+TC followed by administration of GCV via an Alzet pump for 7 days beginning on day 7 (Δ) or day 15 (□). The survival time of both treated groups was significantly longer than that of the untreated control (p = 0.005 for day 7 and p = 0.001 for day 15). For the sake of clarity, the survival times of mice that received either bone marrow alone or unmanipulated lymphocytes are not shown here but are shown in Figure 1. Results from several experiments are combined. The number of mice treated is shown in parentheses by each curve.