Cattle infested with all parasitic life-stages of Boophilus microplus (Canestrini) were treated once with a pour-on formulation of fipronil at 0.25, 0.5, or 1.0% active ingredient (AI) to determine the therapeutic efficacy. Additionally, cattle were infested at weekly intervals for 13 consecutive weeks after treatment to determine the persistent effectiveness of the three concentrations. Results of therapeutic efficacy of fipronil showed that with each increase in concentration there was a corresponding and often significant (P < 0.05) decrease in the numbers, fecundity and fertility of engorged females. The overall control of the Index of Reproduction (IR) achieved at 0.25 and 0.5% AI was 86.2 and 94.3%, respectively, while the control of the IR at the 1.0% AI concentration was 99.7%. The persistent efficacy of fipronil, like the therapeutic efficacy, was also dose related. The 0.25% AI treatment failed to provide complete protection (100%) against larval reinfestation, although control of the IR remained high (> 95%) for the first 6 weeks after treatment. In contrast, at 0.5% AI the control of the IR remained at 100% for the first 4 weeks after treatment, and was > 90% for an additional 2 weeks (6 weeks posttreatment). The 1.0% AI concentration afforded the longest residual activity, providing virtually 100% protection against larval reinfestation for 8 weeks after treatment was applied. Based on the results, neither the 0.25 or 0.5% AI concentration completely eliminated the immature stages of the tick (nymphs and larvae) on the host at the time of treatment (therapeutic efficacy), and the residual activity (persistent efficacy) did not prevent reinfestation by larvae for long periods after treatment. While the 1.0% AI concentration provided both therapeutic and residual efficacy that would be suitable for use in the eradication program, caution is still warranted because a few engorged females detached for up to 25 days after treatment, although none reproduced after the 6th day.