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Total extracts of the aerial parts of four Haplophyllum species (Rutaceae) including Haplophyllum stapfianum Hand.-Mazz., H. tuberculatum (Forssk.) Adr. Juss., H. acutifolium (DC.) G. Don, and H. viridulum Soják were tested for in vitro cytotoxicity against 11 tumor cell lines and normal peripheral blood mononuclear cells (PBMCs). Cytotoxicity of Haplophyllum species were also compared with Ruta graveolens L. (Rutaceae) extract. Cytotoxic activity of extracts was evaluated by the WST-1 assay and expressed as IC50 values. The results obtained indicated that among hematopoietic tumor cell lines, strong cytotoxic activity was observed from H. stapfianum, H. tuberculatum, and H. acutifolium against RAMOS cell line with IC50 values of 12.3, 25.3, and 23.7 µg/mL, respectively; H. stapfianum and H. tuberculatum against U937 cell line with IC50 values of 15.6 and 29.3 µg/mL; and H. tuberculatum against RPMI-8866 cell line with IC50 = 31.8 µg/mL. Testing plant extracts on solid tumor cell lines revealed that all Haplophyllum species have markedly high cytotoxicity against LNCap-FGC-10, a prostate adenocarcinoma cell line, except H. viridulum. H. tuberculatum also showed strong cytotoxic effect against 5637, a bladder carcinoma cell line (IC50 = 23.3 µg/mL). Investigating cytotoxic activity of R. graveolens resulted in higher IC50 values against all tumor cell lines except LNCap-FGC-10 (IC50 = 27.6 µg/mL). Cytotoxicity evaluation of Haplophyllum species on PBMCs revealed that resulting IC50 values for H. stapfianum and H. acutifolium on tumor cell lines with high cytotoxic activity were significantly lower than the IC50 values obtained for PBMCs (p < 0.05). [ABSTRACT FROM AUTHOR]