Rotheca glabrum (formerly known as Clerodendrum glabrum [Verbenaceae]) is used by local communities in the Limpopo Province of South Africa to control ticks on livestock and was selected from the database of the ARC-Onderstepoort Veterinary Institute. Its leaves were extracted using organic solvents ranging from polar to non-polar solvents (methanol, acetone and dichloromethane (DCM)). In addition, the traditional soap-water (infusion) and water-based (decoction) methods were used. The tick repelling activity was determined against the adult stage of the livestock tick Rhipicephalus appendiculatus.In the tick-climbing repellency bioassay a 30% acetone extract had a significant (p ≤ 0.05) repellent effect against adults of R. appendiculatus. The extract was still active at a lower concentration of 10%. The hexane fraction from the R. glabrum acetone extract had a higher tick repellency activity than the positive controls Amitix and Bayticol at the same concentrations. Unfortunately, the activity decreased after 2.5 h, probably due to volatility of the biologically active compound(s) within the extract.Attempts were made to isolate the repellent compound from the acetone extract of R. glabrum. The process produced very good results up to a late stage in the bioassay-guided fractionation process. At that point, the repellent activity was lost. When two fractions were combined, the repellent activity was regained. These results provide strong evidence for the existence of a synergisticactivity of different compounds. It may be better to concentrate on extracts that would kill ticks rather than on extracts that would repel ticks.