One of the most commonly consumed and commercially relevant herbal teas in South Africa is rooibos tea, prepared from the plant, Aspalathus linearis (Burm. F.) Dahlg. In orthodox medicine, antimicrobial agents are amongst the most commonly prescribed groups of drugs and thus there is a considerable possibility for the concurrent use of these drugs with the highly popular beverage, rooibos tea. Therefore, the aim of this study was to investigate the interactive antimicrobial and toxicity profiles of A. linearis (aqueous and organic extract), when combined with seven conventional antimicrobials (ciprofloxacin, erythromycin, gentamicin, penicillin G, tetracycline, amphotericin B and nystatin). The antimicrobial activity of A linearis was evaluated, independently and in combination, using the minimum inhibitory concentration (MIC) assay against two yeasts, three Gram-positive and three Gram-negative bacteria. The interactions were further evaluated using the sum of the fractional inhibitory concentration (Sigma FIC) assessment. Combinations demonstrating notable synergistic or antagonistic interactions were investigated in various ratios (isobolograms). The toxicity of A. linearis extracts and antimicrobials was assessed independently and in combination, using the brine-shrimp lethality assay (BSLA), and the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MU) cell proliferation assay on the human HEK-293 cell line. A. linearis (aqueous and organic extract) with penicillin G demonstrated the most notable interactions, when tested against the Gram-positive bacteria, with Sigma FIC values ranging from 0.01 (synergistic) to 0.94 (additive). Varied ratio studies of this combination were most synergistic against Staphylococcus aureus. Four antagonistic combinations were identified against the Gram-negative bacteria and yeasts. In the BSLA, no combinations were identified to be toxic. However, in the MTT assay, two combinations were found to demonstrate a possible toxic effect (A. linearis aqueous and organic extract with nystatin), with inhibitory effects of 73.76 +/- 3.36% and 56.88 +/- 6.61%, respectively, thus warranting further in vivo studies. (C) 2014 SAAB. Published by Elsevier B.V. All rights reserved.