BACKGROUND: A high HTLV-1 proviral load is found in HTLV-1-associated diseases, mainly HAM/TSP. However, the association between proviral load and keratoconjunctivitis sicca (KCS) has not been well established. AIM: To verify the association between KCS and HTLV-1 proviral load. STUDY DESIGN: 104 HTLV-1 infected patients (51 asymptomatic and 52 with HAM/TSP) from the HTLV reference center in Salvador, Brazil were followed from June 2008 to May 2010. Evaluation of tear secretion was performed by BUT (break-up time), Rose Bengal and Schirmer I tests. The diagnosis of KCS was based upon the presence of symptoms and when at least two of three tests were positive. HTLV-1 proviral load was determined using real-time PCR. RESULTS: The prevalence of KCS was 44.2%. KCS was more frequent among HAM/TSP patients (p = 0.022). Patients with KCS had higher proviral load (mean 134,672 ± 150,393copies/10(6) PBMC) than patients without the disease (mean 66,880 ± 109,525copies/10(6) PBMC) (p = 0.001). HTLV-1 proviral load>100,000copies/10(6) PBMC increased significantly the risk of developing KCS (OR = 4.05 and 95% CI = 1.40-11.76). After age>45 years and HAM/TSP status were excluded in stepway reward analysis, the variables PVL>100,000 (OR = 4.77 and 95% CI = 1.83-12.44) still remained statistically significant. CONCLUSION: HTLV-1 proviral loads are higher in patients with KCS and may represent a relevant biological marker of disease.