Clinical trials on a central Kentucky Thoroughbred Farm (B) during 1960–1961 involved nine test treatments of mares, yearlings and weanlings ( n = 124), and compared efficacies of phenothiazine (PTZ), piperazine (PPZ), mixtures of PTZ+PPZ and thiabendazole (TBZ) for (1) percent reduction and (2) complete clearance or graded reduction of strongyle egg per gram (epg) counts. Three grades of PTZ (N.F. green, micronized purified and 2–3-μm purified) at the dose rate of 55 mg kg −1 were ineffective in six tests; reduction of strongyle epg count were low grade (26%) and complete clearance was found in only 1 of 32 horses. Piperazine alone at 88 mg base kg −1 was efficacious in two tests; epg counts were effectively reduced (98%), but complete clearance was found in only 2 of 10 horses. Several mixtures of PTZ+PPZ with various dosages of PTZ (27.5–55 mg kg −1) plus PPZ base (88 mg kg −1) were quite effective in six tests, as epg counts were reduced by 96% and complete clearance occurred in 25 of 38 horses. Four trials with TBZ at dose rates between 13 and 44 mg kg −1 in 1961 reduced epg counts by 98%, but cleared only 15 of 36 horses. These data indicated: (1) a large segment of the Farm B small strongyle population was resistant to PTZ at the outset of these observations in 1960; (2) TBZ-resistant individuals were also present in this population when TBZ was first used in 1961. During the ensuing 4-year study (1962–1965) on Farm B mares ( n = 15 per year) and yearlings ( n = 15–17 per year), biweekly epg and larvae per gram (lpg) counts were carried out to compare the efficacy of three treatment programs: (1) monthly doses of TBZ at 26 mg kg −1; (2) monthly doses of TBZ at 13 mg kg −1; (3) bimonthly doses of a mixture of PTZ+PPZ and carbon disulfide (CS 2) at dose rates of 27.5+88 and 78 mg kg −1, respectively, or a mixture of PTZ+PPZ+trichlorfon (TCF) at dose rates of 27.5+88+40 mg kg −1, respectively. Emergence of a TBZ-resistant segment of the small strongyle infections was evaluated by three criteria: (1) annual mean strongyle epg counts; (2) efficacy of individual treatments for epg reductions (%); (3) complete clearance or graded reductions of strongyle epg counts. In contrast, treatments with PTZ+PPZ−CS 2 (mares) and PTZ+PPZ+TCF (yearlings) were efficacious. Both drugs produced relatively low average annual egg counts, efficacious reductions in epg counts and high rates of clearance or graded reductions of egg counts. For the latter, PTZ+PPZ−CS 2 was marginally more efficacious ( P < 0.05) than PTZ+PPZ+TCF. Multiple resistance of small strongyles in this population (B) was observed. Prior to 1960, long-term use of PTZ for strongyle control had led to selected PTZ-resistant small strongyles. Initial use of TBZ in 1961 produced effective epg reductions, but complete clearance data revealed the presence of TBZ-resistant small strongyles at the outset. Subsequently, the regimen of regular treatments with TBZ of ∼50% of the mares and yearlings resulted in the increasing dominance over time of the TBZ-resistant segment of the population of small strongyles. The population remained uniformly responsive to treatments with mixtures of PTZ+PPZ−CS 2 or PTZ+PPZ+TCF.