The resistance of Plasmodium falciparum to the chloroquine-proguanil association (C/P) as antimalarial chemoprophylaxis is becoming increasingly common in Africa. Daily oral doxycycline hyclate 100 mg is effective as malaria prophylaxis. But the hyclate salt's adverse effects combined with the capsule's galenic form are incompatible with good chemoprophylaxis compliance. We conducted a randomized group study of 522 French soldiers deployed in Gabon and Chad for 4 months to determine the tolerability of short-term malaria chemoprophylaxis with a 100-mg daily tablet of a monohydrate doxycycline salt compared with a daily C/P capsule. At days 7 and 120, compliance was better in the doxycycline group [respectively 98.5%vs. 73.9% (P < 0.001) and 90.5%vs. 74% (P < 0.001)]. No major event (evacuation, hospitalization) was related to the medications. Epigastralgia, diarrhoea, urticaria, mouth ulcers, sun sensitization and desquamation were significantly more frequent in the C/P group (P < 0.05). There was no statistical difference for malaria incidence, vertigo, nausea and hair loss. These results suggest that doxycycline monohydrate may be safely used in short-term malaria chemoprophylaxis. With the same efficacy as a hyclate doxycycline, doxycycline monohydrate could be a good chemoprophylaxis for short-term travellers at particular risk of C/P resistant P. falciparum malaria.