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Background and Objective: There have been described compelling correlations between mutations in some Plasmodium falciparum genes and resistance to antimalarial drugs. To apply molecular techniques in the mechanisms of epidemiological surveillance in the Hospital Clínic of Barcelona and to map potential levels of resistance, we investigated the presence of mutations in the relevant codons of genes associated with resistance in P. falciparum isolates imported by travellers., Patients and Method: The genes pfctr, pfmdr1, dhfr, dhps and cytochrome b were analyzed by PCR and enzymatic restriction in P. falciparum isolates from 53 persons attending the Tropical Medicine Department after a trip to a malaria endemic area., Results: 63% of patients were infected with a P. falciparum isolate with the K76T mutation in pfctr. Tyr86 in pfmdr1 was found in 54% of the isolates. Mutations in codons 51, 59 and 108 in dhfr were found in 33%, 49% and 44% of the isolates, respectively. Mutations in codons 436, 437 and 540 in dhps were found in 35%, 35% and 8.5% of the isolates. 30% of travellers were infected by parasites displaying 3 or more mutations in any of the codons of dhps and dhfr. None of the patients had a mutation in the Tyr268 codon of the cytochrome B gene., Conclusions: The high prevalence of mutations in the imported isolates suggests a fast development and expansion of resistance against most of the antimalarial drugs commonly used. The concurrence of more than one mutation in different loci suggests the expansion of multiple resistances.