The exon 3-deleted/full-length growth hormone receptor (GHRd3) polymorphism and the collagen type Iα 1-specific protein 1 (COLIA1) polymorphism have each recently been linked to the responsiveness to recombinant growth hormone (GH) treatment in GH-deficient adults. In this context, one or two GHRd3 alleles and the homozygous COLIA1 TT genotype were each associated with a significantly lower GH dose. Aim: The aim of this pilot study was to test if these polymorphisms together have an additive effect on the individually required GH dose in adults with GH deficiency. Patients & methods: The GHRd3 and COLIA1 polymorphisms were determined in 130 German adult patients (65 men, 65 women; mean age: 45.9 years ± 12.9 SD; majority Caucasian) with GH deficiency of different origin, derived from the prospective KIMS Pharmacogenetics Study. Patients received GH treatment for at least 12 months with finished dose-titration of GH and centralized IGF-1 measurements. GH dose after 1 year of treatment, IGF-1 concentrations, IGF-1 standard deviation score and anthropometric data were analyzed according to genotype group. Results: Concerning etiology, gender, age, anthropometric data, IGF-1 concentrations and IGF-1 standard deviation score, study subjects demonstrated no significant differences by genotype. After 1 year of GH treatment, the GH dose in the GH-deficient patients carrying one or two alleles of the growth hormone receptor (GHR) exon 3 deletion and the TT genotype of the COLIA1 polymorphism was on average half the dose required in patients with the full-length GHR (fl/fl) and the homozygous COLIA1 GG genotype (p = 0.045). Conclusion: Carriers of one or two alleles of the GHR exon 3 deletion and COLIA1 TT genotype require significantly lower GH doses as compared with both homozygous fl GHR and COLIA1 GG genotype carriers. There seems to be an additive effect of both polymorphisms on the individually required GH dose in GH-deficient adults which may serve to explain part of the variability of the required amounts of exogenous GH in these patients.