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Introduction: Proton radiation offers physical advantages over conventional radiation. Radiosensitivity of human 59M ovarian cancer and HTB140 melanoma cells was investigated after exposure to gamma-rays and protons. Material and methods: Irradiations were performed in the middle of a 62 MeV therapeutic proton spread out Bragg peak with doses ranging from 2 to 16 Gy. The mean energy of protons was 34.88+/-2.15 MeV, corresponding to the linear energy transfer of 4.7+/-0.2 keV/mu m. Irradiations with gamma-rays were performed using the same doses. Viability, proliferation and survival were assessed 7 days after both types of irradiation while analyses of cell cycle and apoptosis were performed 48 h after irradiation. Results: Results showed that gamma-rays and protons reduced the number of viable cells for both cell lines, with stronger inactivation achieved after irradiation with protons. Surviving fractions for 59M were 0.91+/-0.01 for gamma-rays and 0.81+/-0.01 for protons, while those for HTB140 cells were 0.93+/-0.01 for gamma-rays and 0.86+/-0.01 for protons. Relative biological effectiveness of protons, being 2.47+/-0.22 for 59M and 2.08+/-0.36 for HTB140, indicated that protons provoked better cell elimination than gamma-rays. After proton irradiation proliferation capacity of the two cell lines was slightly higher as compared to gamma-rays. Proliferation was higher for 59M than for HTB140 cells after both types of irradiation. Induction of apoptosis and G2 arrest detected after proton irradiation were more prominent in 59M cells. Conclusions: The obtained results suggest that protons exert better antitumour effects on ovarian carcinoma and melanoma cells than gamma-rays. The dissimilar response of these cells to radiation is related to their different features.