Aim Evaluation of the thermal and physical conditions for inactivation of adenovirus (AdV), porcine sapelovirus 1 (PSV1) and the economically important viruses porcine epidemic diarrhoea virus (PEDV) and porcine circovirus 2 (PCV2) in the production of spray-dried porcine plasma (SDPP). Methods and Results Citrate-treated porcine plasma of pH 7 center dot 5, 9 center dot 8 and 10 center dot 2 (8 center dot 5% dry-matter) was spiked with PEDV, PSV1, PCV2 and AdV and incubated at 3 degrees C for maximum 24 h, and at 44 or 48 degrees C for maximum 10 min (Experiment 1). Spiked citrate-treated concentrated plasma of pH 7 center dot 5 and 9 center dot 8 (24% dry-matter) was spray dried in a laboratory scale apparatus (Experiment 2). Aliquots of SDPP were stored over a period of 0-10 weeks at 11 and 20 degrees C (Experiment 3). Reverse transcription(RT)-quantitative PCR detected no notable reduction in viral genomes in treated plasma and SDPP samples. No infectious PSV1 was re-isolated from plasma and SDPP samples in cell culture. At pH 10 center dot 2 and 3 degrees C, infectivity of PEDV in plasma was reduced with a reduction factor of 4 center dot 2 log 10 (LRF) at 10 h contact time, whereas heating to 44 degrees C for at least 1 min at alkali pH was needed to achieve a LRF of 4 center dot 2 for AdV. Spray drying at an outlet temperature of 80 degrees C reduced AdV infectivity effectively (LRF = 5 center dot 2) and PEDV infectivity for 95% (LRF = 1 center dot 4). After storage at 20 degrees C for 2 weeks no infectious PEDV was re-isolated from SDPP anymore (LRF >= 4 center dot 0). Due to growth of antibiotic-resistant bacteria from plasma in cell cultures used for PCV2 isolation, no data regarding inactivation of PCV2 were obtained. Conclusions Five percent of PEDV stayed infectious after our spray drying conditions. Spray drying in combination with storage for >= 2 weeks at 20 degrees C eliminated infectivity of PEDV effectively. Significance and Impact of the Study The conditions for inactivation of virus in plasma and SDPP determined are important for producers to inactivate PEDV during production of SDPP.